1278 MODE OF ACTION OF 2 - MERCAPTOETttANOI

It has been reported by many authors that a variety of thiol compounds augment various lymphocyte reactions in vitro, including antibody responses (1, 2), induction of cytotoxic T cells in the mixed lymphocyte culture (3, 4), and the DNA synthetic response to mitogens (5-7). 2-Mercaptoethanol (2-ME), 1 one of the most effective thiols, was shown to be a polyclonal activator of both T cells (8) and B cells (9). Although 2-ME is widely used as an effective additive to lymphocyte cultures to elicit in vitro antibody responses, its mechanism of action still remains to be elucidated, particularly at the molecular level. Opitz et al. (10) have proposed that 2-ME does not act directly on lymphocytes, but interacts with fetal calf serum (FCS) to convert its component(s) into activated form, which in turn is directly involved in the augmentation of the primary antibody response to sheep erythrocytes (SRBC) (11). Sidman and Unanue (12) also demonstrated that the enhancing effect of 2-ME was mediated by 2-ME-activated serum factor(s) in anti-Ig antibody-induced proliferation of murine B cells. The chemical nature of these 2-ME-activated factor(s), however, has not been investigated in detail. On the other hand, Goodman et al. (9, 13, 14) have reported that 2-ME could act directly on late-maturing, resting murine lymphocytes, including both T cells and B cells, to trigger their proliferation and differentiation. They have reported (15) that synergistic cooperation between T and B cells was involved in the activation process by 2-ME. It has been recently proposed by Hoffeld and Oppenheim (16) that a major role of 2-ME in the augmentation of antibody response in vitro is to convert oxidized glutathione (GSSG) in the serum into reduced glutathione (GSH). The former compound had inhibitory effect on antibody response, whereas 2-ME was found to reverse its inhibition. Thus, we have no final conclusion as to the mechanism of action of 2-ME. In a previous paper (7), we compared the enhancing activities of various thiol compounds and found that antibody response was markedly augmented by cysteine, which has higher reduction potential than